Is caffeine consumption safe during pregnancy?

I have a pregnant patient who experienced a miscarriage in the past and who has asked me whether her consumption of 2 cups of coffee per day could have caused it. What should I tell her?

ANSWER

There are conflicting data on the fetal safety of dietary caffeine consumption during pregnancy, particularly at levels of 300 mg/d or greater. Although it is difficult to assess the risk of spontaneous abortion with caffeine consumption, most of the data do not suggest an increased risk of adverse pregnancy, fertility, or neurodevelopmental outcomes with caffeine consumption of 300 mg/d or less from all sources. Therefore, consumption of 1 to 2 cups of coffee a day is not expected to be a concern.

There are conflicting data on the fetal safety of dietary caffeine consumption during pregnancy, particularly at levels of 300 mg/d or greater. Although it is difficult to assess the risk of spontaneous abortion with caffeine consumption, most of the data do not suggest an increased risk of adverse pregnancy, fertility, or neurodevelopmental outcomes with caffeine consumption of 300 mg/d or less from all sources. Therefore, consumption of 1 to 2 cups of coffee a day is not expected to be a concern.

Caffeine is one of the most commonly consumed stimulants in the general population. 1 It is found in a variety of foods and beverages, including coffee, tea, chocolate, cocoa products, soft drinks, and energy drinks. In addition, it is increasingly used as an ingredient in prescription and over-the-counter medications for colds, influenza, headache, menstrual symptoms, weight loss, and central nervous system stimulation.

The effects of caffeine on the body are mediated via interaction with a number of receptors, including adenosine, adrenergic, cholinergic γ-aminobutyric acid, and serotonin receptors. 1 The concerns about caffeine use during pregnancy or lactation are owing to the theoretical effects on the fetus: caffeine crosses the placental barrier 2; caffeine's elimination half-life increases in late gestation; and infants poorly metabolize caffeine until 3 months of age. 3

The amount of caffeine in various food and beverage preparations varies.

Table 1 provides common examples of these foods and beverages and the amount of caffeine that might be expected in each. 4 However, because the caffeine content can vary depending on the manufacturer or preparation, one needs to consult specific product information for more detail.

Several critical literature reviews have been conducted on potential associations between caffeine and spontaneous abortion, congenital malformations, and fetal growth restriction. 5-7 These reviews have considered thousands of pregnancies, as well as a variety of study designs, including case-control and cohort studies. Most of these studies did not evaluate women with caffeine consumption greater than 300 mg/d, corresponding to about 3 cups of instant coffee per day. In addition, many methodologic flaws were recognized, such as lack of control for confounders including smoking and alcohol use. 5-7 Smoking is a key concern, as it causes spontaneous abortion, and many women combine coffee consumption with smoking. Overall conclusions include that there is insufficient evidence of a causal association between caffeine use and increase in spontaneous abortions, particularly if less than 300 mg/d is consumed; there is no increased risk of birth defects; and there are insignificant reductions in fetal growth with caffeine consumption of 300 mg/d or less. 5-7

Fertility

A European multicentre study retrospectively collected information on time to conception in 3187 women aged 25 to 44. A significant risk of subfecundity was seen in the first pregnancy for women consuming 500 mg/d or greater of caffeine (odds ratio 1.45, 95% CI 1.03 to 2.04). The authors concluded that high levels of caffeine might delay conception. 7

A literature review of human studies from 2000 to 2009 assessed the effect of caffeine on fertility outcomes including infertility, semen quality, and various end points of assisted reproductive technology. Overall, the authors reported no positive relationship between caffeine consumption and adverse effects on fertility. 8 However, owing to methodologic limitations, more studies are needed to corroborate these data.

A 2010 study also reported no association between caffeine consumption (mean 455 mg/d) and success rate of pregnancy after in vitro fertilization. 9

Neurodevelopmental outcomes

A literature review of studies published between 1975 and 1999 reported minimal effects of caffeine ingestion during pregnancy on neurodevelopment and behaviour in infants and children. 10 However, there have been several cases of caffeine withdrawal reported in infants whose mothers consumed very high amounts of caffeine (greater than 800 mg/d). 10 Overall, the authors concluded that there was little evidence to recommend against consuming moderate amounts of caffeine during pregnancy.

Other studies reported no adverse effects on child behaviour with the consumption of moderate amounts (less than 300 mg/d) of caffeine during pregnancy. 11-13 A cohort study of 885 children born in Brazil demonstrated no increased risk of frequent nocturnal awakening (more than 3 episodes per night) at 3 months postpartum when examining women who consumed an average of 144 mg/d of caffeine. Almost 20% of mothers were heavy caffeine consumers during pregnancy (300 mg/d or greater), and while the incidence of frequent night awakening in children tended to increase, the difference was not significant when compared with those consuming less than 300 mg/d (22.5% vs 13.5%, P = .114). 14

Conclusion

Data about the consumption of caffeine doses of 300 mg/d or less do not suggest increased risk of adverse pregnancy, fertility, or neurodevelopmental outcomes. At this time, the data about caffeine consumption of 300 mg/d or greater are limited and conflicting; therefore, it is best to limit caffeine intake to less than 300 mg/d. The amount of caffeine per cup of coffee varies between products, but as a general rule, consuming 1 to 2 cups of coffee a day is not expected to be a concern.

Motherisk questions are prepared by the Motherisk Team at The Hospital for Sick Children in Toronto, Ont. Ms. Morgan is a doctoral candidate in the Faculty of Pharmacy at the University of Toronto. Dr. Koren is Director and Ms. Bozzo is Assistant Director of the Motherisk Program. Dr. Koren is supported by the Research Leadership for Better Pharmacotherapy during Pregnancy and Lactation. He holds the Ivey Chair in Molecular Toxicology in the Department of Medicine at the University of Western Ontario in London.

Do you have questions about the effects of drugs, chemicals, radiation, or infections in women who are pregnant or breastfeeding? We invite you to submit them to the Motherisk Program by fax at 416 813-7562; they will be addressed in future Motherisk Updates.

Published Motherisk Updates are available on the Canadian Family Physician website (www.cfp.ca) and also on the Motherisk website.

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